TYROSINE

ne of the most investigated amino acids is tyrosine (TYR). TYR is the biochemical precursor of norepinephrine (NE) and dopamine (DA)-which are neurotransmitters of the catecholinergic system-via conversion to L-dopa, the direct precursor of dopamine. Early research has shown that TYR supplementation, or a TYR-rich diet, increases plasma TYR levels in the blood (1) and enhances DA and NE release in the brain (2-4).

Tyrosine hydroxylase, the enzyme involved in the conversion from tyrosine to L-DOPA, is about 75% saturated with tyrosine under typical physiological conditions. As the other enzymes involved in catecholamine synthesis have low saturation rates, there is a modest but significant potential to increase brain catecholamine synthesis by increasing local tyrosine levels. Once the optimal level of DA is reached, TYR is no longer transformed to DA because tyrosine hydroxylase is inhibited (5,6). Previous studies on the effect of TYR on cognition focused mainly on deficits in TYR to DA conversion (e.g. phenylketonuria; 7), on the depletion of TYR (8,9), or on DA-related diseases (e.g. Parkinson’s disease). In healthy individuals, TYR has often been used to reduce the negative effects of conditions that deplete the brain’s dopaminergic resources, such as extreme physical stress. The supply of TYR was found to reduce stress-induced impairments of working memory and attentional tasks, but more so in individuals who were particularly sensitive to the stressors (10-12).

It appears that TYR administration selectively counteracts DA depletion, a process in which performance levels decline corresponding to the decrease DA function in the brain: When exposed to physical stress or a cognitively challenging task, the rate of DA synthesis rises (13). In order to meet the situational demands more DA is synthesized from TYR and L-DOPA. Once these chemical forerunners abate, DA synthesis becomes sparse, causing less DA availability and accordingly decrements in performance (14,15). Under these circumstances, TYR may provide the resources necessary to allow DA synthesis to carry on and DA to remain at a level that allows optimal performance (16). Indeed, TYR supplementation has been found to stimulate DA production in actively firing neurons only (17,18).

The most commonly adopted hypothesis about stress-induced performance decrements holds that reduced brain catecholamine levels account for this phenomenon (19,20). In line with this, tyrosine depletion experiments, in which participants consume an amino acid mixture devoid of tyrosine and its precursor, phenylalanine, suggest that acute reductions in brain catecholamine levels lead people to behave in a less motivated way or develop cognitive impairments. Moreover, reduced brain catecholamine levels seem to make mood more vulnerable to the negative effects of low light exposure. Consequently, positive effects of increased tyrosine intake in demanding situations could be explained by the replenishment of brain catecholamines. In short, selective increases in the intake of tyrosine may benefit those aspects of human behavior and cognition that are under the catecholaminergic control.

 

Tyrosine-cognitive task performance, fatigue and alertness under stressful conditions

A 1996 review on dietary neurotransmitter precursors by Young reported beneficial effects of tyrosine on cognitive task performance, fatigue, and general alertness under various stressful conditions (20). There were no consistent effects on mood, although some case reports and small studies suggested that tyrosine might potentiate the action of antidepressant drugs.

In the only subsequent study to use a longitudinal design, tyrosine or placebo was supplemented for two seasons to research station residents in Antarctica (21). Mood improved in the tyrosine group and worsened in the placebo group over the course of the winter, in the summer the tyrosine group did not differ from the placebo group in terms of mood. As previous research has shown that the detrimental effects of experimental tyrosine depletion on mood are larger in dim light than in bright light (22), one could hypothesize that tyrosine supplementation can exert a larger effect on mood in the absence of sunlight than in its presence, i.e. during the summer. In line with this hypothesis, animal studies suggest that short days increase dopamine turnover in the pituitary (23) and suppress tyrosine hydroxylase expression in the prefrontal cortex. This can help explain why tyrosine is more likely to influence mood during the winter than during the summer.

Only one out of six similarly designed studies found tyrosine to enhance physical performance relative to placebo (24). This suggests that tyrosine loading may not be sufficient to counteract exercise-induced physical fatigue. However, for athletes whose sport requires fine motor skills and a lot of cognitive effort to perform well, tyrosine has greater potential as an effective performance aid. For example, in one study tyrosine was able to acutely protect cold-induced decrements in marksmanship accuracy (18). Moreover, tyrosine loading had consistent effects on working memory and information processing, which suggests that tyrosine could help athletes in sports that demand cognitive and psychomotor performance under difficult conditions, such as biathlon.

Tyrosine could aid performance not only in sports, but also in occupational contexts. When a situation imposes heavy cognitive loads or harsh environmental conditions upon people, tyrosine is able to prevent or reverse the cognitive performance decrements induced by these conditions. As tyrosine can improve convergent thinking (19), in academia tyrosine might help students improve their focus while studying. This suggests that tyrosine might provide an alternative to frequently used “study drugs” such as methylphenidate (25), since the effects of tyrosine loading on working memory and information processing speed appear to be similar to those of methylphenidate (26). Indirect support for the mitigation of performance decrements by tyrosine was obtained by looking at biomarkers of brain functioning in animals (21,27). This suggests that tyrosine might counteract information processing decrements under stressful circumstances.

 

Executive Performance

A recent systematic review using only randomized double-blind, placebo-controlled designs identified 15 studies suitable for inclusion. This suggests that their quality was better than that of the case studies and mostly uncontrolled studies previously described by Young. However, since the total number of selected studies was limited and as their sample sizes were small to moderate, the absence of significant effects of tyrosine on endurance exercise performance in particular were interpreted with caution. Furthermore, some studies used a placebo that was rich in carbohydrates (e.g., orange juice), which may have inadvertently affected brain uptake of tyrosine (28).

The authors concluded “cognitive studies employing neuropsychological measures found that tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load. The buffering effects of tyrosine on cognition may be explained by tyrosine's ability to neutralize depleted brain catecholamine levels. There is evidence that tyrosine may benefit healthy individuals exposed to demanding situational conditions”.

 

Cognitive function

Indeed, only lately, has the focus shifted to the possible beneficial effects of TYR on challenging cognitive performance in the absence of physical stress. Here, even without exposure to stress, the supplementation of TYR has been shown to have an acute beneficial effect on challenging task performance thought to be related to DA, such as multitasking, the updating and monitoring of working memory, stopping on time, and convergent thinking (29-31).

Recently researchers investigated whether TYR promotes cognitive flexibility, a cognitive-control function that Is assumed to be modulated by DA (32). They tested the effect of TYR on proactive vs. reactive control during task switching performance, which provides a relatively well-established diagnostic of cognitive flexibility. In a double-blind, randomized, placebo-controlled design, 22 healthy adults performed in a task-switching paradigm. Compared to a neutral placebo, TYR promoted cognitive flexibility (i.e. reduced switching costs). This finding supports the idea that TYR can facilitate cognitive flexibility by repleting cognitive resources.

Hence it appears increased tyrosine intake is able to combat the decrements in working memory, slowed information processing, and worsening of mood that might be induced by physically or mentally demanding situations. Moreover, even in the absence of extreme conditions, tyrosine may improve convergent thinking. Taken together, the available observations provide converging evidence for the idea that the amino-acid TYR is a promising cognitive enhancer that facilitates cognitive flexibility.

 

References

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14. Muly III,E.C.,Szigeti,K.,Goldman-Rakic,P.S.,1998.D1 receptor in interneurons of macaque prefrontal cortex: distribution and subcellular localization. J.Neurosci. 18,10553–10565.

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18. O'Brien, C., Mahoney, C., Tharion, W.J., Sils, I.V., Castellani, J.W., 2007. Dietary tyrosine benefits cognitive and psychomotor performance during body cooling. Physiol. Behav. 90, 301-307

19. Colzato, L.S., Jongkees, B.J., van den Wildenberg, W.P.M., Hommel, B., 2014b. Eating to stop: tyrosine supplementation enhances inhibitory control but not response execution. Neuropsychologia 62, 398e402.

20. Young SN. Behavioral effects of dietary neurotransmitter precursors: basic and clinical aspects. Neuroscience & Biobehavioral Reviews. 1996 Dec 31;20(2):313-2

21. Palinkas LA, Reedy KR, Smith M, Anghel M, Steel GD, Reeves D, Shurtleff D, Case HS, Do NV, Reed HL. Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged Antarctic residence. International journal of circumpolar health. 2007 Dec 1;66(5):402-17.

22. Cawley EI, Park S, Aan Het Rot M, Sancton K, Benkelfat C, Young SN, Boivin DB, Leyton M. Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder. Journal of psychiatry & neuroscience: JPN. 2013 Nov;38(6):388.

23. Steger RW, DePaolo L, Asch RH, Silverman AY. Interactions of Δ9-tetrahydrocannabinol (THC) with hypothalamic neurotransmitters controlling luteinizing hormone and prolactin release. Neuroendocrinology. 1983;37(5):361-70.

24. Tumilty, L., Davison, G., Beckmann, M., Thatcher, R., 2011. Oral tyrosine supplementation improves exercise capacity in the heat. Eur. J. Appl. Physiol. 111,2941-2950.

25. Babcock Q, Byrne T. Student perceptions of methylphenidate abuse at a public liberal arts college. Journal of American college health. 2000 Nov 1;49(3):143-5.

26. Linssen AM, Riedel WJ, Sambeth A. Effects of tyrosine/phenylalanine depletion on electrophysiological correlates of memory in healthy volunteers. Journal of Psychopharmacology. 2011 Feb;25(2):230-8.

27. Kishore, K., Ray, K., Anand, J.P., Thakur, L., Kumar, S., Panjwani, U., 2013. Tyrosine ameliorates heat induced delay in event related potential P300 and contingent negative variation. Brain Cognit. 83, 324e329

28. Wurtman RJ, Wurtman JJ, Regan MM, McDermott JM, Tsay RH, Breu JJ. Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. The American journal of clinical nutrition. 2003 Jan 1;77(1):128-32.

29. Colzato, L.S., De Haan, A., Hommel, B., 2014. Food for creativity: tyrosine promotes performance in a convergent-thinking task. Psychol. Res. 79, 709e714.

30. Colzato, L.S., Jongkees, B.J., Sellaro, R., Hommel, B., 2013. Working memory reloaded: tyrosine repletes updating in the N-back task. Front. Behav. Neurosci. 7, 200.

31. Colzato, L.S., Jongkees, B.J., van den Wildenberg, W.P.M., Hommel, B., 2014. Eating to stop: tyrosine supplementation enhances inhibitory control but not response execution. Neuropsychologia 62, 398e402

32. Steenbergen L, Sellaro R, Hommel B, Colzato LS. Tyrosine promotes cognitive flexibility: evidence from proactive vs. reactive control during task switching performance. Neuropsychologia. 2015 Mar 31;69:50-5.